Journal of Interferon and Cytokine Research最新文献

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LINC00641/miR-378a and Their Cross-Talk with TNF-α/IFN-γ as Potential Biomarkers in Ulcerative Colitis and Crohn's Diseases. LINC00641/miR-378a及其与TNF-α/IFN-γ的交互作用作为溃疡性结肠炎和克罗恩病的潜在生物标志物
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-11-01 DOI: 10.1089/jir.2023.0097
Nour A Abdel Hameed, Olfat G Shaker, Nabil A Hasona
{"title":"LINC00641/miR-378a and Their Cross-Talk with TNF-α/IFN-γ as Potential Biomarkers in Ulcerative Colitis and Crohn's Diseases.","authors":"Nour A Abdel Hameed, Olfat G Shaker, Nabil A Hasona","doi":"10.1089/jir.2023.0097","DOIUrl":"10.1089/jir.2023.0097","url":null,"abstract":"<p><p>The most well-known forms of inflammatory bowel disease (IBD) that affect the entire gastrointestinal tract are ulcerative colitis (UC) and Crohn's disease (CD). The serum profile of inflammatory biomarkers and noncoding RNA and their role in the propagation of the inflammatory process remains controversial. Thus, this study was designed to examine the relationship between hematological profile, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), and the expression of LINC00641 and miR-378a in individuals with IBDs. In addition, we elucidated the correlation between the expression of LINC00641 and miR-378a and the biochemical variables analyzed. This retrospective study analyzed 94 unrelated participants. Group I included healthy controls, Group II consisted of participants diagnosed with UC, and Group III consisted of participants diagnosed with CD. Patients with IBDs experienced significant elevations in CRP, total leukocyte count, platelets, erythrocyte sedimentation rate, TNF-α, and INF-γ. However, participants with IBD had lower hemoglobin and albumin levels than healthy control participants. Moreover, the expression levels of LINC00641 and miR-378a were elevated in participants with IBD, with a significant difference between participants with IBD and healthy controls. The most striking observation was a clear association between serum LINC00641 and miR-378a levels and the biochemical variables assessed. This study demonstrated a positive correlation between the expression of LINC00641/miR-378a and TNF-α in patients with UC and CD patients. This study suggests that LINC00641 and miR-378a are prospective biomarkers and noninvasive screening tools for IBDs, which may help predict the progression of complications.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 11","pages":"531-537"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Many Faces of Oligoadenylate Synthetases. 低聚腺苷酸合成酶的多面性。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-11-01 Epub Date: 2023-09-25 DOI: 10.1089/jir.2023.0098
Saumendra N Sarkar, Munesh K Harioudh, Lulu Shao, Joseph Perez, Arundhati Ghosh
{"title":"The Many Faces of Oligoadenylate Synthetases.","authors":"Saumendra N Sarkar, Munesh K Harioudh, Lulu Shao, Joseph Perez, Arundhati Ghosh","doi":"10.1089/jir.2023.0098","DOIUrl":"10.1089/jir.2023.0098","url":null,"abstract":"<p><p>2'-5' Oligoadenylate synthetases (OAS) are interferon-stimulated genes that are most well-known to protect hosts from viral infections. They are evolutionarily related to an ancient family of Nucleotidyltransferases, which are primarily involved in pathogen-sensing and innate immune response. Classical function of OAS proteins involves double-stranded RNA-stimulated polymerization of adenosine triphosphate in 2'-5' oligoadenylates (2-5A), which can activate the latent RNase (RNase L) to degrade RNA. However, accumulated evidence over the years have suggested alternative mode of antiviral function of several OAS family proteins. Furthermore, recent studies have connected some OAS proteins with wider function beyond viral infection. Here, we review some of the canonical and noncanonical functions of OAS proteins and their mechanisms.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"487-494"},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41122431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Annihilation of Non-small Cell Lung Cancer by NKG2D CAR-T Cells Produced from T Cells from Peripheral Blood of Healthy Donors. 健康供体外周血T细胞产生的NKG2D CAR-T细胞对非小细胞肺癌癌症的杀伤作用。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 DOI: 10.1089/jir.2023.0043
Jinhong Jiang, Yonghua Liu, Yuxiao Zeng, Bingmu Fang, Yongping Chen
{"title":"Annihilation of Non-small Cell Lung Cancer by NKG2D CAR-T Cells Produced from T Cells from Peripheral Blood of Healthy Donors.","authors":"Jinhong Jiang,&nbsp;Yonghua Liu,&nbsp;Yuxiao Zeng,&nbsp;Bingmu Fang,&nbsp;Yongping Chen","doi":"10.1089/jir.2023.0043","DOIUrl":"10.1089/jir.2023.0043","url":null,"abstract":"<p><p>Some progress has been made in immunotherapy with chimeric antigen receptor (CAR)-T cells targeting NKG2D-NKG2DL with the purpose of eradicating solid tumors. Non-small cell lung cancer (NSCLC) has been shown to express NKG2DL. This study hence evaluated the therapeutic effect of NKG2D CAR-T cells on NSCLC. Accordingly, NKG2D CAR-T cells were obtained from diverse human autologous T cell sources. T cells from peripheral blood T lymphocytes of healthy volunteers (without NKG2D CAR insertion) were used as NT-T cells. Coculture of effector cells (CAR-T cells or NT-T cells) with target cells (NSCLC cells such as PC-9 or NCL-H460 cells) was performed at different ratios. The cytotoxicity of CAR-T cells was examined using lactate dehydrogenase assay kits. Murine xenograft assay was conducted to investigate the <i>in vivo</i> antitumor effect of CAR-T cells. Cytokines secreted from CAR-T cells were assessed by enzyme-linked immunosorbent assay. CAR-T cell infiltration into xenografts was observed through immunochemical assay. Based on the results, NKG2DL was highly expressed in NSCLC cells. Compared with NT-T cells, NKG2D CAR-T cells from different sources of T cells delivered stronger toxicity, and secreted more effector and memory function-related cytokines to NSCLC cells, and those from the peripheral blood of healthy donors (H-T cells) exhibited the strongest effect. Furthermore, compared with NT-T cells, H-T cells and NKG2D CAR-T cells from NSCLC patients' peripheral blood diminished tumor, improved survival, increased body weight and tumor-infiltrating capacity, and upregulated serum IFN-γ level in NOG mice. Collectively speaking, NKG2D CAR-T cells exhibit a robust effect on eradicating NSCLC in a NKG2DL-dependent manner, thus making themselves a promising therapeutic candidate for NSCLC patients.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"445-454"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Conversation with Judy Lieberman. 与朱迪·利伯曼的对话。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 DOI: 10.1089/jir.2023.29055.int
{"title":"A Conversation with Judy Lieberman.","authors":"","doi":"10.1089/jir.2023.29055.int","DOIUrl":"10.1089/jir.2023.29055.int","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"441-444"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role and Potential Regulatory Mechanism of STING Modulated Macrophage Apoptosis and Differentiation in Severe Acute Pancreatitis-Associated Lung Injury. STING调节巨噬细胞凋亡和分化在严重急性胰腺炎相关肺损伤中的作用及其潜在调控机制。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 DOI: 10.1089/jir.2023.0077
Yiqiu Peng, Yingying Li, Yuxi Yang, Tingjuan Shi, Ruixia Liu, Yingyi Luan, Chenghong Yin
{"title":"The Role and Potential Regulatory Mechanism of <i>STING</i> Modulated Macrophage Apoptosis and Differentiation in Severe Acute Pancreatitis-Associated Lung Injury.","authors":"Yiqiu Peng,&nbsp;Yingying Li,&nbsp;Yuxi Yang,&nbsp;Tingjuan Shi,&nbsp;Ruixia Liu,&nbsp;Yingyi Luan,&nbsp;Chenghong Yin","doi":"10.1089/jir.2023.0077","DOIUrl":"10.1089/jir.2023.0077","url":null,"abstract":"<p><p>This study aims to investigate the role of STING in promoting macrophage apoptosis and regulating macrophage polarization in severe acute pancreatitis (SAP)-associated lung injury <i>in vitro</i> and <i>in vivo</i>. A murine model was established by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). Meanwhile, ANA-1 cells were stimulated with LPS to induce apoptosis <i>in vitro</i>. More primary alveolar macrophages underwent apoptosis and M1 macrophage polarization in the SAP group compared with the control group, which was reversed by inhibiting STING. When ANA-1 cells were induced into M2-type macrophages, the reduction of M1 macrophage markers was accompanied by a decrease of LPS-induced apoptosis. Finally, the inhibitory effect of C-176 on STING ameliorates lung injury and inflammation by adjusting macrophage polarization and rescuing apoptosis. Therefore, inhibiting STING could be a new therapeutic strategy for treating acute pancreatitis-associated lung injury.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"455-468"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Call for Special Issue Papers: The "Yin-Yang" Activities of Tumor-Induced Inflammatory Cytokines for Cancer Immunotherapy, Detection and Prognosis. 特刊论文征集:癌症免疫治疗、检测和预后肿瘤诱导炎症细胞因子的“阴阳”活性。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 DOI: 10.1089/jir.2023.29056.cfp
Yan Ma, Sanjay Mukherjee, Jing Ma
{"title":"<i>Call for Special Issue Papers:</i> The \"Yin-Yang\" Activities of Tumor-Induced Inflammatory Cytokines for Cancer Immunotherapy, Detection and Prognosis.","authors":"Yan Ma, Sanjay Mukherjee, Jing Ma","doi":"10.1089/jir.2023.29056.cfp","DOIUrl":"10.1089/jir.2023.29056.cfp","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"439-440"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA-Dependent Interferon Induction and Lung Inflammation in Bordetella pertussis Infection. 百日咳杆菌感染中DNA依赖性干扰素的诱导和肺部炎症。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 Epub Date: 2023-08-31 DOI: 10.1089/jir.2023.0066
Jeremy Ardanuy, Karen M Scanlon, Ciaran Skerry, Nicholas H Carbonetti
{"title":"DNA-Dependent Interferon Induction and Lung Inflammation in <i>Bordetella pertussis</i> Infection.","authors":"Jeremy Ardanuy, Karen M Scanlon, Ciaran Skerry, Nicholas H Carbonetti","doi":"10.1089/jir.2023.0066","DOIUrl":"10.1089/jir.2023.0066","url":null,"abstract":"<p><p>Pertussis, caused by <i>Bordetella pertussis</i>, is a resurgent respiratory disease but the molecular mechanisms underlying pathogenesis are poorly understood. We recently showed the importance of type I and type III interferon (IFN) induction and signaling for the development of lung inflammation in <i>B. pertussis</i>-infected mouse models. Classically, these IFNs are induced by signaling through a variety of pattern recognition receptors (PRRs) on host cells. Here, we found that the PRR signaling adaptor molecules MyD88 and TRIF contribute to IFN induction and lung inflammatory pathology during <i>B. pertussis</i> infection. However, the PRRs Toll-like receptors (TLR) 3 and TLR4, which signal through TRIF and MyD88, respectively, played no role in IFN induction. Instead, the DNA-sensing PRRs, TLR9 and STING, were important for induction of type I/III IFN and promotion of inflammatory pathology, indicating that DNA is a major inducer of lung IFN responses in <i>B. pertussis</i> infection. These results increase our understanding of this host-pathogen interaction and identify potential targets for host-directed therapies to reduce <i>B. pertussis</i>-mediated pathology.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"478-486"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals. 急性和康复新冠肺炎患者IL-10细胞因子家族的特征。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 Epub Date: 2023-09-14 DOI: 10.1089/jir.2023.0075
Anuradha Rajamanickam, Pavan Kumar Nathella, Nandhini Selvaraj, Murhekar Manoj, Jeromie Wesley Vivian Thangaraj, Santhosh Kumar Muthusamy, Girish Kumar Chethrapilly Purushothaman, Tarun Bhatnagar, Manickam Ponnaiah, Sabarinathan Ramasamy, Saravanakumar Velusamy, Subash Babu
{"title":"Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals.","authors":"Anuradha Rajamanickam,&nbsp;Pavan Kumar Nathella,&nbsp;Nandhini Selvaraj,&nbsp;Murhekar Manoj,&nbsp;Jeromie Wesley Vivian Thangaraj,&nbsp;Santhosh Kumar Muthusamy,&nbsp;Girish Kumar Chethrapilly Purushothaman,&nbsp;Tarun Bhatnagar,&nbsp;Manickam Ponnaiah,&nbsp;Sabarinathan Ramasamy,&nbsp;Saravanakumar Velusamy,&nbsp;Subash Babu","doi":"10.1089/jir.2023.0075","DOIUrl":"10.1089/jir.2023.0075","url":null,"abstract":"<p><p>Cytokines are major players in orchestrating inflammation, disease pathogenesis, and severity during COVID-19. Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses to various inflammatory and infectious diseases. However, the role of the IL-10 family of cytokines in COVID-19 remains elusive. Hence, we determined the plasma levels of the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, and IL-24) in 7 groups of COVID-19 individuals, based on days since real-time reverse transcriptase-polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data show that the levels of IL-10, IL-19, IL-20, IL-22, and IL-24 cytokines decreased from days 15-30 to days 61-90 and plateaued thereafter. Severe COVID-19 patients exhibit increased plasma levels of IL-10, IL-19, IL-20, IL-22, and IL-24 compared to mild patients. Thus, our study provides evidence of alterations in the plasma levels of the IL-10 family of cytokines in convalescent COVID-19 individuals.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"469-477"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10245043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815. 从人干扰素Lambda 4 TT等位基因rs368234815表达一种新的具有恢复阅读框的非活性异构体。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-03-07 DOI: 10.1089/jir.2022.0199
Seema Bharatiya, Aditya Agarwal, Sreedhar Chinnaswamy
{"title":"A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815.","authors":"Seema Bharatiya, Aditya Agarwal, Sreedhar Chinnaswamy","doi":"10.1089/jir.2022.0199","DOIUrl":"10.1089/jir.2022.0199","url":null,"abstract":"<p><p>The TT allele of the dinucleotide variant rs368234815 (TT/ΔG) abolishes the open reading frame (ORF) created by the ancestral ΔG allele of the human interferon lambda 4 (<i>IFNL4</i>) gene, thus preventing the expression of a functional IFN-λ4 protein. While probing the expression of IFN-λ4 in human peripheral blood mononuclear cells (PBMCs), using a monoclonal antibody that binds to the C-terminus of IFN-λ4, surprisingly, we observed that PBMCs obtained from TT/TT genotype individuals could also express proteins that reacted with the IFN-λ4-specific antibody. We confirmed that these products did not emanate from the <i>IFNL4</i> paralog, IF1IC2 gene. Using cell lines and overexpressing human <i>IFNL4</i> gene constructs, we obtained evidence from Western blots to show that the TT allele could express a protein that reacted with the IFN-λ4 C-terminal-specific antibody. It had a molecular weight similar if not identical to IFN-λ4 expressed from the ΔG allele. Furthermore, the same start and stop codons used by the ΔG allele were used to express the novel isoform from the TT allele suggesting that a restoration of the ORF had occurred in the body of the mRNA. However, this TT allele isoform did not induce any IFN-stimulated gene expression. Our data do not support a ribosomal frameshift that leads to the expression of this new isoform, implying that an alternate splicing event may be responsible. An N-terminal-specific monoclonal antibody did not react with the novel protein isoform suggesting that the alternate splicing event likely occurs beyond exon 2. The new isoform is glycosylated similar to the functional IFN-λ4 and is also secreted. Furthermore, we show that the ΔG allele can also potentially express a similarly frameshifted isoform. The splicing event that leads to the generation of these novel isoforms and their functional significance remains to be elucidated.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"370-378"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia. 干扰素Lambda受体的缺失阐明了对小鼠胆道闭锁模型的易感性。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 DOI: 10.1089/jir.2023.0046
Stephen J Hartman, Madeleine A Weiss, Haley M Temple, Bryan Donnelly, Rajamouli Pasula, Holly M Poling, Monica McNeal, Sujit K Mohanty, Greg M Tiao
{"title":"Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia.","authors":"Stephen J Hartman, Madeleine A Weiss, Haley M Temple, Bryan Donnelly, Rajamouli Pasula, Holly M Poling, Monica McNeal, Sujit K Mohanty, Greg M Tiao","doi":"10.1089/jir.2023.0046","DOIUrl":"10.1089/jir.2023.0046","url":null,"abstract":"<p><p>Biliary atresia (BA) is a life-threatening cholangiopathy occurring in infancy, the most common indication for pediatric liver transplantation. The etiology of BA remains unknown; however, a viral etiology has been proposed as multiple viruses have been detected in explants of infants afflicted with BA. In the murine model of BA, Rhesus rotavirus (RRV) infection of newborn BALB/c pups results in a cholangiopathy that mirrors human BA. Infected BALB/c pups experience 100% symptomatology and mortality, while C57BL/6 mice are asymptomatic. Interferon-λ (IFN-λ) is an epithelial cytokine that provides protection against viral infection. We demonstrated that IFN-λ is highly expressed in C57BL/6, leading to reduced RRV replication. RRV-infection of C57BL/6 IFN-λ receptor knockout (C57BL/6 IFN-λR KO) pups resulted in 90% developing obstructive symptoms and 45% mortality with a higher viral titer in bile ducts and profound periportal inflammation compared to C57BL/6. Histology revealed complete biliary obstruction in symptomatic C57BL/6 IFN-λR KO pups, while C57BL/6 ducts were patent. These findings suggest that IFN-λ is critical in preventing RRV replication. Deficiency in IFN-λ permits RRV infection, which triggers the inflammatory cascade causing biliary obstruction. Further IFN-λ study is warranted as it may play an important role in infant susceptibility to BA.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"427-434"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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